This chapter provides a review of prevalence and trends of resistance in Campylobacter jejuni and Campylobacter coli isolated from humans in different parts of the world and a more thorough description of the mechanisms of resistance, origin, spread, and clinical consequences of resistance. Aminoglycosides exhibit rapid and significant bactericidal effects in vitro and should initially be included for the treatment of Campylobacter bacteremia in patients who appear very ill. The only mechanism of chloramphenicol resistance identified in Campylobacter occurs through modification of chloramphenicol by chloramphenicol acetyltransferase, which prevents its binding to the ribosome. The majority of contacts between Tet(O) and the ribosome are mediated by the rRNA, and one interaction with ribosomal protein S12. Most of the antimicrobials used in veterinary medicine are tetracyclines and macrolides, which result in high and continuous selective pressure for the animal-colonizing bacteria, ultimately resulting in the acquisition of antimicrobial resistance genes. Investigation into the mechanisms of action of antimicrobials, as well as the transfer of resistance determinants, is necessary to gain effective control of antimicrobial resistance. Epidemiological and microbiological studies show that poultry is the most important source for quinolone-susceptible and quinolone-resistant Campylobacter infections in humans. Trends over time for macrolide resistance show stable low rates in most countries, and macrolides should remain the drug class of choice for C. jejuni and C. coli enteritis.

Quinolone resistance rates (in percentages) among C. jejuni (Denmark, The Netherlands, and Norway) and C. jejuni and C. coli combined (Finland, Sweden, the United Kingdom, and the United States) by history of travel. Data are from references 7, 11, 25, 47, 84, 139, and 143.

10.1128/9781555817534/fig16-2_thmb.gif

10.1128/9781555817534/fig16-2.gif

Figure 2.

Quinolone resistance rates (in percentages) among C. jejuni (Denmark, The Netherlands, and Norway) and C. jejuni and C. coli combined (Finland, Sweden, the United Kingdom, and the United States) by history of travel. Data are from references 7, 11, 25, 47, 84, 139, and 143.

(A) Elongation cycle of protein synthesis; (B) inhibition by tetracycline (Tc); (C) model for Tet(O) action. (A) In the absence of antibiotics, the aa-tRNA–EF-Tu–GTP ternary complex catalyzes the binding of aa-tRNA to the open A site on the pretranslocation-state (Pre) ribosome. (B) Tc initially binds to the posttranslation-state (Post) ribosome and induces a conformational change (or steric clash) that blocks the aa-tRNA–EF-Tu–GTP ternary complex from occupying the A site, effectively inhibiting further protein synthesis. (C) If Tet(O) is present, it recognizes the Tc-blocked ribosome by virtue of its open A site, prolonged pausing, and possibly by a drug-induced conformational change. The interaction of Tet(O) with the ribosome induces rearrangements in the A site and triggers the release of Tc from the primary binding site prior to GTP hydrolysis. Tet(O) then hydrolyzes the bound GTP and likely leaves the ribosome with the GTPase-associated region in a configuration compatible with EF-Tu binding, thereby allowing protein synthesis to continue. Adapted from references 36 and 37.

10.1128/9781555817534/fig16-3_thmb.gif

10.1128/9781555817534/fig16-3.gif

Figure 3.

(A) Elongation cycle of protein synthesis; (B) inhibition by tetracycline (Tc); (C) model for Tet(O) action. (A) In the absence of antibiotics, the aa-tRNA–EF-Tu–GTP ternary complex catalyzes the binding of aa-tRNA to the open A site on the pretranslocation-state (Pre) ribosome. (B) Tc initially binds to the posttranslation-state (Post) ribosome and induces a conformational change (or steric clash) that blocks the aa-tRNA–EF-Tu–GTP ternary complex from occupying the A site, effectively inhibiting further protein synthesis. (C) If Tet(O) is present, it recognizes the Tc-blocked ribosome by virtue of its open A site, prolonged pausing, and possibly by a drug-induced conformational change. The interaction of Tet(O) with the ribosome induces rearrangements in the A site and triggers the release of Tc from the primary binding site prior to GTP hydrolysis. Tet(O) then hydrolyzes the bound GTP and likely leaves the ribosome with the GTPase-associated region in a configuration compatible with EF-Tu binding, thereby allowing protein synthesis to continue. Adapted from references 36 and 37.

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